Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling.
Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling.
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DOI：
10.1038/nn.3892
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发表时间：
2015-01
影响因子：
25
通讯作者：
Katona, Istvan
中科院分区：
文献类型：
--
作者：
Dudok, Barna;Barna, Laszlo;Ledri, Marco;Szabo, Szilard I.;Szabadits, Eszter;Pinter, Balazs;Woodhams, Stephen G.;Henstridge, Christopher M.;Balla, Gyula Y.;Nyilas, Rita;Varga, Csaba;Lee, Sang-Hun;Matolcsi, Mate;Cervenak, Judit;Kacskovics, Imre;Watanabe, Masahiko;Sagheddu, Claudia;Melis, Miriam;Pistis, Marco;Soltesz, Ivan;Katona, Istvan
神经科学中的一个主要挑战是以细胞类型和亚细胞室特有的方式确定信号分子的纳米级位置和数量。因此，我们开发了一种结合细胞特定的生理和解剖学特征与超分辨率成像的新方法，并研究了影响小鼠海马区突触内大麻素信号生理特性的分子和结构参数。我们发现，与树突投射的中间神经元相比，周向投射的GABA能中间神经元的轴突终末具有更多的CB1受体数量、活动区复杂性和受体/效应器比，这与体细胞突触与树突突触的大麻样信号的更高效率是一致的。此外，长期给予GABA9-四氢大麻酚降低了大麻素对Δ释放的影响，并以剂量依赖的方式引起CB1的显著下调。在停止Δ9-四氢大麻酚治疗几周后，受体需要完全恢复。这些发现表明，对内源性蛋白在大脑回路中的分布进行特定细胞类型的纳米级分析是可能的，并识别控制内源性大麻信号和大麻诱导的认知功能障碍的新的分子特性。
A major challenge in neuroscience is to determine the nanoscale position and quantity of signaling molecules in a cell-type-, and subcellular compartment-specific manner. We therefore developed a novel approach combining cell-specific physiological and anatomical characterization with superresolution imaging, and studied the molecular and structural parameters shaping the physiological properties of synaptic endocannabinoid signaling in the mouse hippocampus. We found that axon terminals of perisomatically-projecting GABAergic interneurons possess increased CB1 receptor number, active-zone complexity, and receptor/effector ratio compared to dendritically-projecting interneurons, in agreement with higher efficiency of cannabinoid signaling at somatic versus dendritic synapses. Furthermore, chronic Δ9-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked dramatic CB1-downregulation in a dose-dependent manner. Full receptor recovery required several weeks after cessation of Δ9-tetrahydrocannabinol treatment. These findings demonstrate that cell-type-specific nanoscale analysis of endogenous protein distribution is possible in brain circuits, and identify novel molecular properties controlling endocannabinoid signaling and cannabis-induced cognitive dysfunction.
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影响因子：
16.2
作者：
Frank, Thomas;Rutherford, Mark A.;Strenzke, Nicola;Neef, Andreas;Pangrsic, Tina;Khimich, Darina;Fetjova, Anna;Gundelfinger, Eckart D.;Liberman, M. Charles;Harke, Benjamin;Bryan, Keith E.;Lee, Amy;Egner, Alexander;Riedel, Dietmar;Moser, Tobias
通讯作者：
Moser, Tobias
影响因子：
16.2
作者：
Dani, Adish;Huang, Bo;Bergan, Joseph;Dulac, Catherine;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
56.9
作者：
Bates, Mark;Huang, Bo;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
25
作者：
Carlson, G;Wang, Y;Alger, BE
通讯作者：
Alger, BE
影响因子：
2
作者：
Hoffman, Alexander F.;Oz, Murat;Lupica, Carl R.
通讯作者：
Lupica, Carl R.